Tag Archives: Pharm

Zofran

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Well here is the study that has had everyone talking for a while. Good old ondansetron category B now may cause congential malformations in the fetus. This study in the journal Reproductive Toxicology retrosp of 1349 infants concludes a risk for CV defect (septum specifically) is increased to a statistically significant degree. My favorite prior study looked at 608,000 pregnancies and concluded no malformation risk. This is in the NEJM. So I am much more likely to follow the recs of the huge NEJM study.

Now we could do more prospective studies of course to see if ondansetron is causing any true effects. And we can always use the promethazine, prochlorperazine class of drugs in these patients while in the ED or even for discharge. I still love good old extremely evidence-based ginger pills, also B6, diphenhydramine, not eating crap food, etc.

Discussion is welcome.

2015 ACLS GUIDELINES

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The new 2015 ACLS guidelines were published this month!  I love new guidelines!  I’ve highlighted the important drug stuff (you guys are on your own for the rest).

Vasopressin: REMOVED FROM ALGORITHM: This was no surprise to me as vasopressin has never been shown to offer any advantage over epinephrine in studies to date.

“Vasopressin offers no advantage as a substitute for epinephrine in cardiac arrest (Class IIb, LOE B-R)”

“Vasopressin in combination with epinephrine offers no advantage as a substitute for standard-dose epinephrine in cardiac arrest (Class IIb, LOE B-R)”

Steroids: I’ve been skeptical of the use of steroids in cardiac arrest since 2009 inhospital cardiac arrest trial (steroids were combined with a vasopressor bundle or cocktail of epi and vasopressin).  Will need much more convincing data before I’ll recommend routine use- and that is exactly what our guidelines endorse as well.  Because: no one in the ICU dies before receiving a course of steroids.  The pre-hospital use of steroids is pretty clear: no benefit.

“In IHCA, the combination of intra-arrest vasopressin, epinephrine, and methylprednisolone and post-arrest hydrocortisone as described by Mentzelopoulos et al may be considered; however, further studies are needed before recommending the routine use of this therapeutic strategy (Class IIb, LOE C-LD)”

“For patients with OHCA, use of steroids during CPR is of uncertain benefit (Class IIb, LOE C-LD)”

Epinephrine: Nothing groundbreaking here.  A few trials did demonstrate ROSC advantage with high-dose epi over standard dose; however, no improvement in survival to discharge (emphasis on good neurologic recover) over standard dose.  There is much concern with adverse effects of higher dose epi in the post-arrest period which may negate potential advantages during intra-arrest period.

“Standard-dose epinephrine (1 mg every 3 to 5 minutes) may be reasonable for patients in cardiac arrest (Class IIb, LOE B-R)”

“High-dose epinephrine is not recommended for routine use in cardiac arrest (Class III: No Benefit, LOE B-R)”

Antiarrhythmics: Really no changes.  Emphasized use of amiodarone over lidocaine (which is not new).

“Amiodarone may be considered for VF/pVT that is unresponsive to CPR, defibrillation, and a vasopressor therapy (Class IIb, LOE B-R)”

“Lidocaine may be considered as an alternative to amiodarone for VF/pVT that is unresponsive to CPR, defibrillation, and vasopressor therapy (Class IIb, LOE C-LD)”

“The routine use of magnesium for VF/pVT is not recommended in adult patients (Class III: No Benefit, LOE B-R)”

Circulation 2015:132:S444-64

Antibiotic review

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Maybe it’s because an overhead projector slide scanned and inserted into a powerpoint presentation comprised my medical school antibiotics curriculum (you know what I’m talking about if you went to U of L), but I’ve never really felt comfortable with the nuances of antibiotics. For those who want to understand them a little better, here’s a great review.

The bar is set, Chrissy!

Hot off the Press, Droperidol is Still Safe

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Yet another quality article illustrating the safety of the most magical drug, droperidol. Not sure where people are getting it, as it is not being manufactured currently. We have none at any of my hospitals in Louisville. It is sad but perhaps someday we will get it back. In the same Annals issue an indictment of professional societies, journal editorial boards, and government advisory committees with their misinterpretation of “so-called facts.” Great reading, Dr Newman is the man.

RLQ pain and N/V

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15 yr male with hx of hemophilia presenting with 1 day hx of progressively worsening RLQ pain, decreased PO, nausea, and vomiting. Described RLQ as a “small swelling’ that continued to span across the R abdomen as the day progressed. Denies dysuria, hematuria, hematemesis, hematochezia, constipation, diarrhea, abd trauma, or testicular pain. No previous abdominal surgeries. Physical exam is significant for RUQ and RLQ tenderness, no obvious swelling, no ecchymosis seen. He definitely appeared ill and uncomfortable. A&Ox4.

So already…what are we considering?  Appendicitis …. Peritoneal bleed … bowel obstruction …maybe a few others (UTI, Kidney Stones, STI).

While waiting on CT Abd/Pelvis imaging to be completed, patient is found to be anemic with a Hgb of 8. Normal WBCs. Platelets: 300. Elevated PTT: 83. Normal PT/INR. Urinalysis…. negative. IV Fluids have already been started. Zofran for his continued nausea.

Here’s a significant snapshot of the CT

Abdomen

———————

It spanned from the R kidney down to the bladder. Actively extravasating. Hydronephrosis due to the hematoma compressing the R ureter. It compressed the R renal vasculature as well, and anteriorly displaced the R kidney.

Contacted Hematology, where we decided to administer FEIBA. (He usually takes Alphanate MWF, but had not taken any medicine on day of presentation. Plus, the hospital did not have his particular medication, so we needed to find an alternative.) He was admitted to the Hematology service. They have plans of contacting Surgery for any possible interventions once his Hgb stabilized.

Repeat CBC (after patient had been admitted) showed that the Hgb had fallen to 6.0.

Diagnosis: 15 year old male with non-traumatic R retro peritoneal hematoma. Source currently unknown.

A-fib with RVR + sepsis + hypotension = conundrum

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How do we slow the rate without lowering the BP? Will slowing the rate even help the BP? How do we raise the BP without speeding up the rate?

The patient who inspired this post came in for a bowel obstruction. Cards was initially consulted for possible new a-fib, but there really wasn’t much to do from a cardiac standpoint. THEN he perforated his bowel and went for emergency surgery, where he required pressors and went into a-fib with RVR. He was packed open and taken to the SICU, where he was hypotensive to SBP 70s, tachycardic to 160s, and intermittently hypoxic.

If you want to skip my thoughts on the case and head straight for the facts, here is an interesting article about a-fib in critically ill patients. It talks about the various options for management and the pros/cons of each.

If expert opinion is more your style, try this.

Of course, there is also controversy around slowing down a-fib when it is caused by sickness. Should we let the body do its thing to try and compensate? Here’s one article that suggests maybe we shouldn’t get so hung up on rate control in sick people.

Now back to the case. The surgery resident and I were of the mind that slowing the rate and organizing the rhythm should help with cardiac output. There are several reasons why this logic still seems to be in the majority.

– With a-fib you lose atrial kick. That little extra oomph from the atrium may not seem like a big deal, but it can have a significant impact on cardiac output. Here’s a fun article from 1965 that shows a 53% increase in cardiac output from converting a-fib to sinus (using quinidine because 1965). The results have obviously been redemonstrated in more recent studies, but how often do you get to reference quinidine? Not that often.

– Diastolic filling is important for stroke volume. With any tachyarrhythmia, less diastolic filling time means lower stroke volume. However people who do “math” would argue that increasing the rate would likely keep cardiac output about the same. This logic holds up with regular rhythms, but studies show that irregular rhythm decreases cardiac output compared to regular rhythm. Here’s one such study.

– In real life, we went for amiodarone and electrical cardioversion. From the a-fib in critical care article above, it seems like that’s still the best option.
Here’s a good article I wish I had read before embarking on a cluster of a cardioversion. P.S. Put the pads on correctly. Anterior-posterior pads definitely worked better for this 350 pound patient. Anterior pads = fail x3. AP pads = success!

– It’s worth noting that this is not one of the scenarios when you’re worrying about giving someone a stroke with cardioversion. This guy’s risk of death was much greater than his risk of stroke.

Another consideration for this situation was the choice of pressors. Eventually the patient ended up maxed on pretty much all pressors, but that may not always be the case.

Surviving Sepsis guidelines are all about Levophed as a first line pressor, which is usually a great option. But guidelines are just guidelines. How many of our patients are otherwise 100% healthy and just have a little sepsis? Not that many.

– In this case, I think phenylephrine may have been a better first option. Pure alpha agonist activity vasoconstricts without Levophed’s cardiac effects, which probably didn’t do us any favors with the RVR.

– Based on the EMCrit blog above it also seems like phenylephrine might have allowed us to use a beta blocker without worrying about blocking the effects of the pressor or a calcium channel blocker without exacerbating hypotension. Thoughts?

– Anyone have other ideas about pressors in this scenario?

There was a lot more to the case after that, but this post has already ended up way longer than I intended. In the end, it was a 350 pound unhealthy guy with a less than ideal heart, so unfortunately, his family ended up withdrawing care. I doubt anything we could have done would have changed his outcome, but maybe there’s something to learn from it that will help someone else someday. I’ve talked to several people about this case and gotten different opinions from each one, so I figure why not open it up for a few more opinions to really confuse clear things up.

Everything including the lipid sink

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80+ yo gentleman with PMH of COPD, CHF, CAD, CKD, initially hospitalized for urosepsis and NSTEMI with a worsening AKI, and baseline CKD. Tuned him up and sent him to the floor where he accidentally received an overdose of his carvedilol. Got the call that the patient was hypotensive to 70s systolic, bradycardic to 30s.

Immediately pacer pads were placed to ward off evil spirits
-Started with 1L crystalloid bolus –> no response and with risk factors and pmhx, didn’t want to fluid overload
-Tried atropine (3-4 doses) –> no response
-Tried glucagon 50mcg/kg loading dose followed by 3mg/hr infusion –> still no luck and exhausted all the glucagon in the pharmacy
Running out of options here. I remember reading an article in Annals about using lipid infusions in beta blocker overdoses and figured it was worth a shot.

Started 20% Intralipid bolus through central line at 1.5ml/kg followed by 0.25ml/kg/min for 30min. Maybe it was the lipid infusion or just the combined effects of everything but by 6am, pt’s BP and HR had improved to normal limits and he began talking again.
It was a nice result but one I couldn’t celebrate that much – within a week, patient decided to go to palliative care and that was the last I heard of him.

PEM Chronicles: Rasburicase

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     A case I saw  last month led me to utilizing a drug I’d never heard of before in the ED: Rasburicase.

     The drug: a recombinant urate oxidase enzyme, which converts existing uric acid to allantoin. This is key due to the higher solubility of allantoin in urine. Patients with Tumor Lysis Syndrome are at risk of acute renal failure due to precipitation of uric acid crystals in renal tubules and collecting ducts.

The case: a 12 yo F with no PMHx who was transferred from an urgent care center for multiple tender, enlarged lymph nodes and a WBC count of 98.

As we worked her up for a new presentation of a hematologic malignancy, it became evident she fit into the parameters for TLS. Initial uric acid level – 14.5 along with hyperkalemia, elevated serum LDH, and hyperphosphatemia. When Hem/Onc came on board, once labs were back, the first recommendations were hydration and Rasburicase.

Provided below is the article I found that informed me on the treatment and a few key points picked up when using it.

For kids only – The drug hasn’t been approved in the US for adults.

G6PD deficiency – Yes, from the depths of med school knowledge, this condition is a contraindication to using Rasburicase. The hydrogen peroxide it produces as a byproduct can lead to hemolysis. Ask if there is a family history.

Coordinating with pharmacy – Due to the preparation of rasburicase, it should be administered immediately after it has been prepared. IV access should be obtained well in advance.

Type of IV access – In our case, hem/onc was considering emergent dialysis. It may be prudent to discuss this with your consultants to get a head-start on what they’ll need once going upstairs.

Not at your medical facility, a specialized pediatric hospital, or somewhere with this in stock??? As you transfer, consider:

1.) Aggressive IV Hydration. Easy to start getting this started, especially if transporting to the next hospital will require hours instead of blocks.

2.) Allopurinol. Though it isn’t required when Rasburicase is given, allopurinol can’t decrease what is already present, but it can help prevent the formation of more uric acid.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1200736/

The Kitchen Sink

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Fairly early into an overnight shift the radio goes off.  EMS is approximately 6min out with mid 30s male undergoing CPR. Per bystanders, the patient was going running from door to door, banging on doors and yelling for help. Shortly after being taken into police custody he was found to be pulseless. Had been undergoing CPR approx 10 min. King airway in place. No improvement with dextrose and naloxone.

The intern on and myself go to Room 9 to get set up. When EMS arrives about 10 minutes later, CPR is still ongoing and rhythm has been asytole/PEA throughout. The story remains consistent with him going from door to door yelling for help but now there is some variation as to whether he was cuffed and then lost his pulse, was found without a pulse, or if he got into a physical altercation with the neighbor and then lost pulse shortly after arrest. There are no signs of trauma and we elected to not invite additional chaos by calling a Level 1.

CPR is continued. King airway switched out for ETT. Accucheck 250’s. Central venous access and bilateral chest tubes placed with no rush of air or blood. Sats persist at 85% on vent, etco2 is in 60’s. He gets epi q3m. A dose of vasopressin and steroids. Istat has K 5.5. Lactate >20. Received 2-3 amps of bicarb. Received calcium. Upon rhythm checks he was primarily asystole except for 2-3 checks with a narrow pea that would not persist. Each time the ultrasound was placed on his heart there was no cardiac activity. My thought process at this time was that he was either excited delirium that I’m not going to be able to do much about or some kind of ingestion/overdose. We called pharmacy and asked for lipid emulsion. His ETCO2 had remained between 40-60 and we were about 40 minutes out from reported time of arrest. I decided if the lipids were unsuccessful that would be when we would call it.

They arrived about 15 minutes later and were infused. By now his etco2 had drifted down to 10 on the most recent pulse check. No changes occurred and TOD was called.

Changes to tPA Contraindications in Acute Ischemic Stroke

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Since its approval in 1987, controversy has surrounded a drug that we all know is near and dear to my heart, recombinant tissue Plasminogen Activator (insert eye roll).  In similar discreetness of a Hollywood wedding, the FDA updated the prescribing information of tPA with important changes made to the contraindications to the use of tPA in the setting of acute ischemic stroke.  It is unclear as to what prompted these updates and why.  There have been no recent studies of significance published to support these modifications.

 

2/2015 updated prescribing info:

“Do not administer Activase to treat acute ischemic stroke in the following situations in which the risk of bleeding is greater than the potential benefit:

• Current intracranial hemorrhage

• Subarachnoid hemorrhage

• Active internal bleeding

• Recent (within 3 months) intracranial or intraspinal surgery or serious head trauma

• Presence of intracranial conditions that may increase the risk of bleeding (e.g., some neoplasms, arteriovenous malformations, or aneurysms)

• Bleeding diathesis

• Current severe uncontrolled hypertension”

 

Now contrast the new package insert to the 2013 package insert.  Pay special attention to the omissions of the exclusion of contraindications in patients with history of intracranial hemorrhage and seizure at onset of stroke.   It is pertinent to note that the wording regarding the contraindications has also changed.  The previous consequences being “significant disability or death” have now been replaced with “situations in which the risk of bleeding is greater than the potential benefit.”

 

From the 2013 package insert (changes are italicized):

“Activase therapy in patients with acute ischemic stroke is contraindicated in the following situations because of an increased risk of bleeding, which could result in significant disability or death:

  • Evidence of intracranial hemorrhage on pretreatment evaluation
  • Suspicion of subarachnoid hemorrhage on pretreatment evaluation
  • Recent (within 3 months) intracranial or intraspinal surgery, serious head trauma, or previous stroke
  • History of intracranial hemorrhage
  • Uncontrolled hypertension at time of treatment (e.g., > 185 mm Hg systolic or > 110 mm Hg diastolic)
  • Seizure at the onset of stroke
  • Active internal bleeding
  • Intracranial neoplasm, arteriovenous malformation, or aneurysm
  • Known bleeding diathesis including but not limited to:

o       Current use of oral anticoagulants (e.g., warfarin sodium) or an International Normalized Ratio (INR) > 1.7 or a prothrombin time (PT) > 15 seconds

o       Administration of heparin within 48 hours preceding the onset of stroke and have an elevated activated partial thromboplastin time (aPTT) at presentation.

o       Platelet count < 100,000/mm3”

 

The new 2/2015 update does provide some vague conditions in which the risks of bleeding must be outweighed against the anticipated benefits (however, note that these are not firm contraindications):

• Recent major surgery or procedure, (e.g., coronary artery bypass graft, obstetrical delivery, organ biopsy, previous puncture of noncompressible vessels)

• Cerebrovascular disease

• Recent intracranial hemorrhage

• Recent gastrointestinal or genitourinary bleeding

• Recent trauma

• Hypertension: systolic BP above 175 mm Hg or diastolic BP above 110 mm Hg

• High likelihood of left heart thrombus, e.g., mitral stenosis with atrial fibrillation

• Acute pericarditis

• Subacute bacterial endocarditis

• Hemostatic defects including those secondary to severe hepatic or renal disease

• Significant hepatic dysfunction

• Pregnancy

• Diabetic hemorrhagic retinopathy, or other hemorrhagic ophthalmic conditions

• Septic thrombophlebitis or occluded AV cannula at seriously infected site

• Advanced age [see Use in Specific Populations (8.5)]

• Patients currently receiving anticoagulants (e.g., warfarin sodium)

• Any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location.

 

Currently the guidelines have not updated their list of contraindications to tPA in acute stroke, but I wouldn’t be surprised to see them included when the guidelines are updated.

 

So like Oprah says, you get tPA! You get tPA! Everyone gets tPA!

Ketofol losing sexiness

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I rarely use ketofol at Jewish, but will let you guys use it at UL when you want. But this article gives a similar opinion to mine: Ketofol does not hold much benefit if any over Ketamine or Propofol.

For quick procedures where you want muscle relaxation (joint reductions or cardioversion), I use propofol. For painful procedures and trauma patients (traction pins, intubating marginal BP patients, chest tubes) I prefer ketamine.

Propofol with the K does NOT seem to decrease emergence reactions. Though Midazolam does so do give 1-2mg midazolam with your ketamine.

My main issue is anecdotally that the ketofol duration of sedation is noticeably shorter than ketamine. I believe this is due to a lower ketamine dose. And we all know that once the dissociative threshold of ketamine is reached, higher doses simply lengthen the duration of effect. You can’t get “more dissociated” just like you can’t be “very unique.”

I don’t even want to mention etomidate here, as I see only one indication for etomidate (as of 2015 where we are on the brink of taking the head injury stigma away from ketamine).

Article is worth a read.